A Randomized, Double-Blind, Placebo-Controlled, Titration-to-Effect Study of Orally Administered CR845 in Patients With Osteoarthritis of the Hip or Knee
Overview
- Phase
- Phase 2
- Intervention
- CR845 tablet 1 mg
- Conditions
- Osteoarthritis, Hip
- Sponsor
- Cara Therapeutics, Inc.
- Enrollment
- 761
- Locations
- 1
- Primary Endpoint
- Change From Baseline at Week 8 With Respect to the Weekly Mean of the Daily 24-hour Pain Intensity for the Index Joint as Measured by the Numeric Rating Scale (NRS).
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The study schedule consists of a Screening Period (up to 14 days), a blinded 4- week Titration-to-Effect Period with weekly visits, a blinded 4-week Maintenance Treatment Period at the optimal dose level determined for each patient, and a 1-week Follow-up Period.
Eligible patients will be randomized to receive either CR845 or placebo in a 2:1 ratio. Every patient will be started on a 1-mg dose of CR845 or matching placebo. During the post-randomization Titration-to-Effect period, the dose of study drug may be increased to 2.5 mg or 5 mg in a double-blind fashion. Patients may know their dose is being changed but will not know whether they were randomization to active study drug or placebo. Approximately 330 patients will be enrolled in this study.
Detailed Description
This is a multicenter, randomized, double-blind, placebo-controlled, titration-to-effect study of orally administered CR845 in patients with osteoarthritis of the hip or knee. The study schedule consists of a Screening Period (up to 14 days), a blinded 4- week Titration-to-Effect Period with weekly visits, a blinded 4-week Maintenance Treatment Period at the optimal dose level determined for each patient, and a 1-week Follow-up Period. Eligible patients will be randomized to receive either CR845 or placebo in a 2:1 ratio. Randomization will be stratified based on a patient's primary OA joint (knee vs. hip). Every patient will be started on a 1-mg dose of CR845 or matching placebo. During the post-randomization Titration-to-Effect period, the dose of study drug may be increased to 2.5 mg or 5 mg in a double-blind fashion. Patients may know their dose is being changed but will not know whether they were randomized to active study drug or placebo. Approximately 330 patients will be enrolled in this study. During the Screening, Titration-to-Effect and Follow-up Period, pain intensity scores will be obtained at specified time points. Blood sampling and safety assessments will be conducted during this period as well. The use of rescue medication for the treatment of any pain (including but not limited to headache, menstrual cramps, or non-target joint pain) during the study will be discussed with the patients at the Screening Visit. Acetaminophen is the only allowable rescue medication for pain beginning from Day -5 until the end of the Maintenance Treatment Period. Starting at the Screening Visit Acetaminophen will be provided as 325-mg tablets and its use (number of tablets taken in the previous 24 hours) will be reported each evening in the patient diary.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntarily provides written informed consent to participate in the study prior to any study procedures.
- •Is able to speak, read, and communicate clearly in English or Spanish; is able to understand the study procedures.
- •Male or female ≥ 25 years of age.
- •Body mass index (BMI) ≤ 40 kg/m
- •Has OA of the hip or knee according to American College of Rheumatology (ACR) criteria.
- •Reports an average pain intensity level ≥ 5 in the index joint at Screening on a 0-10 NRS scale.
- •Is either opioid-naïve (defined as taking \< 10 mg a day of morphine equivalent 14 days prior to screening) or opioid-experienced. If receiving opioid analgesic medication for OA, patients must be on a stable dose ≤ 40 mg of morphine equivalents for 14 days prior to screening.
- •Willing to discontinue currently used pain medications beginning 5 days prior to the Baseline Visit and throughout the study. Acetaminophen use is allowed. (Section 8.8)
- •Of childbearing potential - the patient must be willing to practice an acceptable form of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence from sexual intercourse) for the duration of treatment and for at least 3 days following the last dose of study drug.
- •Of non-childbearing potential - the patient must be surgically or biologically sterile (hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or postmenopausal for at least 1 year).
Exclusion Criteria
- •Inclusion Criteria:
- •A patient will be eligible for enrollment if the following criteria are met:
- •Voluntarily provides written informed consent to participate in the study prior to any study procedures.
- •Is able to speak, read, and communicate clearly in English or Spanish; is able to understand the study procedures.
- •Male or female ≥ 25 years of age.
- •Body mass index (BMI) ≤ 40 kg/m
- •Has OA of the hip or knee according to American College of Rheumatology (ACR) criteria.
- •Reports an average pain intensity level ≥ 5 in the index joint at Screening on a 0-10 NRS scale.
- •Is either opioid-naïve (defined as taking \< 10 mg a day of morphine equivalent 14 days prior to screening) or opioid-experienced. If receiving opioid analgesic medication for OA, patients must be on a stable dose ≤ 40 mg of morphine equivalents for 14 days prior to screening.
- •Willing to discontinue currently used pain medications beginning 5 days prior to the Baseline Visit and throughout the study. Acetaminophen use is allowed. (Section 8.8)
Arms & Interventions
CR845 tablet 1 mg
Dosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.
Intervention: CR845 tablet 1 mg
CR845 tablet 2.5 mg
Dosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.
Intervention: CR845 tablet 2.5 mg
CR845 tablet 5 mg
Dosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.
Intervention: CR845 tablet 5 mg
Placebo tablet
Dosing twice a day (BID) for a total of 8 weeks, with each dose administered at least 2 hours prior to or after a meal.
Intervention: Placebo tablet
Outcomes
Primary Outcomes
Change From Baseline at Week 8 With Respect to the Weekly Mean of the Daily 24-hour Pain Intensity for the Index Joint as Measured by the Numeric Rating Scale (NRS).
Time Frame: Baseline, Week 8
11-point NRS scale where 0 = no pain, and 10= pain as bad as you can imagine
Secondary Outcomes
- Proportion of Patients With at Least 30% Improvement From Baseline in the Weekly Mean Pain Intensity at Week 8(Week 8)
- Proportion of Patients With at Least 50% Improvement From Baseline in the Weekly Mean Pain Intensity at Week 8(Week 8)
- Proportion of Patients Whose OA Pain Was "Very Much Improved" or "Much Improved" as Indicated by Patient Global Impression of Change (PGIC) Score at Week 8(Week 8)
- Average Daily Number of Acetaminophen Tablets Used During Entire Study(Week 8)
- Proportion of Patients Withdrawing From Treatment Due to Lack of Analgesic Efficacy(Week 8)
- Change From Baseline in the WOMAC Stiffness Sub-scale Score at Week 8(Baseline, Week 8)
- Change From Baseline in the Western Ontario & McMaster Osteoarthritis (WOMAC) Index Total Score at Week 8(Baseline, Week 8)
- Change From Baseline in the WOMAC Function Sub-scale Score at Week 8(Baseline, Week 8)
- Change From Baseline in the WOMAC Pain Intensity Sub-scale Score at Week 8(Baseline, Week 8)